Neisseria meningitidis (meningococcus) is a Gram negative human pathogen that causes meningococcal disease, including meningitis and bacterial septicemia induced shock that affect children and young adults ((a) Y. L. Tzeng, D. S. Stephens, Microbes Infect 2000, 2, 687-700; b) M. Virji, Nat Rev Microbiol 2009, 7, 274-286). Vaccines for protecting against meningococcal disease include polysaccharide based vaccines, protein vaccines, and meningococcal outer membrane vesicle (OMV) vaccines.
Based on the surface capsular oligosaccharides of the organism, 13 serogroups of N. meningitidis have been identified, among which A, B, C, Y, and W135 are the major pathogenic strains (N. E. Rosenstein, B. A. Perkins, D. S. Stephens, T. Popovic, J. M. Hughes, N Engl J Med 2001, 344, 1378-1388; b) D. S. Stephens, FEMS Microbiol Rev 2007, 31, 3-14). Group A is the pathogen most often implicated in seasonal epidemic disease in developing countries of Asia and sub-Saharan Africa (M. Achtman, Trends Microbiol 1995, 3, 186-192). Serogroups B and C cause majority of the cases in industrial countries, such as United States of America and other developed countries (D. S. Stephens, B. Greenwood, P. Brandtzaeg, Lancet 2007, 369, 2196-2210). Serogroups W135 and Y are responsible for the remaining cases in the developed countries.
The capsular polysaccharide plays an important role in the bacterial pathogenesis; its antiphagocytic properties help the bacteria to escape from antibody and complement deposition (a) M. R. Spinosa, C. Progida, A. Tala, L. Cogli, P. Alifano, C. Bucci, Infect Immun 2007, 75, 3594-3603; b) M. C. Schneider, R. M. Exley, S. Ram, R. B. Sim, C. M. Tang, Trends Microbiol 2007, 15, 233-240). On the other hand, the unique structures of the capsular polysaccharide also make a good target for vaccine design. Currently, the major source of polysaccharide for vaccine preparation is from acidic lysis of bacteria and column chromatography purification (A. Bardotti, G. Averani, F. Berti, S. Berti, C. Galli, S. Giannini, B. Fabbri, D. Proietti, N. Ravenscroft, S. Ricci, Vaccine 2005, 23, 1887-1899). Due to the limit of purification, the obtained polysaccharide is heterogeneous; therefore, the vaccine quality is inconsistent. Therefore, there remains a need for developing capsular polysaccharides for homogeneous vaccines.